We used a multi-functional mesoporous silica nanoparticle (MSNP) carrier to overcome doxorubicin (Dox) resistance in a multidrug resistant (MDR) human breast cancer xenograft by co-delivering Dox and siRNA that targets the P-glycoprotein (Pgp) drug exporter. The Pgp siRNA selection from among a series of drug resistance targets was achieved by performing high throughput screening in a MDR breast cancer cell line, MCF-7/MDR. Following the establishment of a MCF-7/MDR xenograft model in nude mice, we demonstrated that a 50 nm MSNP, functionalized by a polyethyleneimine-polyethylene glycol (PEI-PEG) copolymer, provides protected delivery of stably bound Dox and Pgp siRNA to the tumor site. The effective biodistribution and reduced reticuloendothelial uptake as a result of our nanocarrier design, allowed us to achieve an 8% enhanced permeability and retention effect at the tumor site. Compared to free Dox or the carrier loaded with either drug or siRNA alone, the dual delivery system resulted in synergistic inhibition of tumor growth in vivo. Analysis of multiple xenograft biopsies demonstrated significant Pgp knockdown at heterogeneous tumor sites, which correspond to the regions where Dox was released intracellularly and induced apoptosis. We emphasize that the heterogeneity originates in the tumor microenvironment, which influence the vascular access, rather than heterogeneous Pgp expression in the MDR cells. Taken together, these data provide proof-of-principle testing of the use of a dual drug/siRNA nanocarrier to overcome Dox resistance in a xenograft. The study also provides the first detailed analysis of the impact of heterogeneity in the tumor microenvironment on the efficacy of siRNA delivery in vivo.

Direct conversion of light into mechanical work, known as the photomechanical effect, is an emerging field of research, largely driven by the development of novel molecular and polymeric material systems. However, the fundamental impediment is that the previously explored materials and structures do not simultaneously offer fast and wavelength-selective response, reversible actuation, low-cost fabrication and large deflection. Here, we demonstrate highly versatile photoactuators, oscillators and motors based on polymer/single-walled carbon nanotube bilayers that meet all the above requirements. By utilizing nanotubes with different chirality distributions, chromatic actuators that are responsive to selected wavelength ranges are achieved. The bilayer structures are further configured as smart 'curtains' and light-driven motors, demonstrating two examples of envisioned applications.

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